Processes for linking a cephalosporin, via the 3-position thereof, to a quinolone, also via the 3-position thereof, have been described in European Patent Application Publication No. 0 251 330, published July 1, 1988. The processes described therein employ a cephalosporin compound having a halomethyl substituent in the 3-position and an ester protected carboxylic acid group in the 2-position. The described processes also employ as a starting material the salt (e.g. a sodium salt) of a quinolone compound in which the salt is formed with the 3-carboxylic acid substituent of the quinolone.
The above-described cephalosporin and quinolone starting materials are then reacted to form a compound in which the cephalosporin and quinolone compounds are linked at their respective 3-positions via an ester linkage of the formula, ##STR2## The described reaction is accompanied by a migration of the .DELTA..sup.3 -double bond in some of the cephalosporin compounds to the .DELTA..sup.2 -position. This results in a mixture of .DELTA..sup.3 and .DELTA..sup.2 isomers
These isomers are not easily separated by chromatographic methods nor by crystallization.
Additionally, the 3-halomethyl cephalosporin compounds may decompose under the reaction conditions and the yields of the desired cephalosporin-quinolone esters are correspondingly low.
A need, therefore, exists for a process of combining a cephalosporin compound with a quinolone compound via an ester linkage where the desired .DELTA..sup.3 -cephalosporinquinolone compound is produced in higher yields than so far have been attainable and wherein production of the unwanted .DELTA..sup.2 -isomer is negligible. A need also exists for a process meeting the above requirements which does not require the use of chromatographic separation techniques to obtain the desired purified .DELTA..sup.3 -isomer.